Ancestral Groups Research Articles

Performance of Polygenic Risk Scores for Primary Open-Angle Glaucoma in Populations of African Descent

ImportancePrimary open-angle glaucoma (POAG) polygenic risk scores (PRSs) continue to be evaluated in primarily European-ancestry populations despite higher prevalence and worse outcomes in African-ancestry populations.ObjectiveTo evaluate how established POAG PRSs perform in African-ancestry samples from the Genetics in Glaucoma Patients of African Descent (GIGA), Genetics of Glaucoma in Individuals of African Descent (GGLAD), and Million Veteran Program (MVP) datasets and compare these with European-ancestry samples.Design, Setting, and ParticipantsThis was a multicenter, cross-sectional study of POAG cases and controls from Tanzania, South Africa, Nigeria, Ghana, and the US. Included were individuals of African descent from South Africa and Tanzania from the GIGA dataset; individuals of African descent from Ghana, Nigeria, and the US from the GGLAD dataset; and individuals of African or European descent from the US in the MVP dataset. Data were analyzed from January 2022 to July 2023.ExposuresThree PRSs derived from large meta-analyses of European and Asian populations, namely Gharahkhani et al (Gharahkhani PRS), Han et al (Han PRS), and Craig et al (Craig PRS).Main Outcomes and MeasuresOdds ratios (ORs) for POAG risk stratification comparing the highest and lowest quintiles; area under the receiver operating characteristic curve (AUROC), and liability coefficient of determination (R2) for the addition of PRS to a baseline of age, sex, and first 5 principal components.ResultsA total of 11 673 cases and 66 432 controls were included in this study across 7 ancestral groups. Mean (SD) age of the total participants was 76.9 (8.7) years, with 74 304 males (95.1%). The following were included in each dataset: GIGA (663 cases, 476 controls), GGLAD (1471 cases, 1482 controls), and MVP (9559 cases, 64 474 controls). Increases in ORs were found for the highest POAG risk quintile ranging from an OR of 1.68 (95% CI, 1.17-2.43) in Ghanaians to 7.05 (95% CI, 2.73-19.6) in the South African multiple ancestry group (which derives from at least 5 distinct ancestral groups: Khoisan, Bantus, Europeans, Indians, and Southeast Asians) with the Gharahkhani PRS. The Han PRS showed OR increases for the highest POAG risk quintile ranging from 2.27 (95% CI, 1.49-3.47) in African American individuals in the GGLAD dataset to 7.24 (95% CI, 6.47-8.12) in Europeans. The Craig PRS predicted OR increases in the highest quintile for all groups ranging from 1.51 (95% CI, 1.05-2.18) in Ghanaians to 6.31 (95% CI, 5.67-7.04) in Europeans. However, AUROC and R2 increases above baseline were lower for all African-ancestry compared with European-ancestry groups in the 3 tested PRSs.Conclusions and RelevanceIn this cross-sectional study, despite some improvements in OR-based risk stratification using the Gharahkhani PRSs, Han PRSs, and Craig PRSs, consistently lower improvements in AUROC and R2 for African-ancestry compared with European-ancestry groups highlight the need for risk prediction models tailored to diverse populations.

First fossil mountain midges (Diptera, Deuterophlebiidae) and their evolutionary and ecological implication

We present here the first-ever fossil flies from the family Deuterophlebiidae. The recent adults have an exceptionally brief lifespan, with males surviving only two hours. Their distinctive features include a complete reduction of mouthparts, and wing venation characterized by a dense net of false veins replacing most of true veins. Due to this distinctive venation the phylogenetic position of Deuterophlebiidae was unclear, compounded by the absence of fossils that could shed light on the early development of these characters. Two new genera and species are described from Burmese amber, Protodeuterophlebia oosterbroeki Krzemiński, Krzemińska & Soszyńska, gen. et sp. nov. and Cretodeuterophlebia courtneyi, Krzemiński, Skibińska & Kopeć, gen. et sp. nov. They date back the age of the family to the mid-Cretaceous. Notably, the fossils reveal first false veins and reduced mouthparts, suggesting a short lifespan in these Cretaceous mountain midges. A comparative analysis of wing venation indicated the Hennigmatidae as a plausible ancestral group to the Deuterophlebiidae. A syninclusion of mayfly indicates the coexistence of these short-lived insects during the same flight period. This synchrony extends to their brief time in flight aligning with the flow of fluid resin. The occurrence of these simultaneous events is extremely low, emphasizing the significance of these findings.

Traces of Paleolithic expansion in the Nivkh gene pool based on data on autosomal SNP and Y chromosome polymorphism.

The Nivkhs are a small ethnic group indigenous of the Russian Far East, living in the Khabarovsk Territory and on Sakhalin Island, descending from the ancient inhabitants of these territories. In the Nivkhs, a specific Sakhalin-Amur anthropological type is prevalent. They are quite isolated, due to long isolation from contacts with other peoples. The gene pool of the Nivkhs and other Far Eastern and Siberian populations was characterized using a genome-wide panel of autosomal single-nucleotide polymorphic markers and Y chromosome haplogroups. Bioinformatic processing of frequencies of autosomal SNPs, Y chromosome haplogroups and YSTR haplotypes showed that the Nivkh gene pool is very different from the other populations'. Analysis of the SNP frequencies using the PCA method divided the Far Eastern populations in full accordance with the territories of their residence into the northern group of the Chukchi and Koryaks and the southern group, including the Nivkhs and Udege. The remoteness of the Nivkhs coincides with their geographic localization, with the Nivkhs and Udege demonstrating the greatest kinship. The Nivkhs have a specific component of their gene pool, which is present with much less frequency in the Udege and Transbaikal Evenks. According to the IBD blocks, the genotypes of the Nivkhs show a very small percentage of coincidence with the Udege, Koryaks, Evenks and Chukchi, the value of which is the lowest compared to the IBD blocks among all other Siberian populations. The Nivkh-specific composition of haplogroups and YSTR haplotypes was shown. In the Nivkhs, the C2a1 haplogroup is divided into three sublines, which have a fairly ancient origin and are associated with the ancestors of modern northern Mongoloids. The Nivkh haplogroup O2a1b1a2a-F238 is found among residents of China and Myanmar. The Q1a1a1-M120 line is represented among the Nivkhs, Koryaks, Evenks and Yukaghirs. Phylogenetic analysis of individual Y chromosomal haplogroups demonstrated the closeness of the Nivkh gene pool with the ancient population of the Amur and Okhotsk regions, the Koryaks, the Tungus peoples and the population of Southeast Asia. The Nivkh gene pool confirms the relative smallness of their ancestral groups without mixing with other populations.

Heterogeneity-aware integrative regression for ancestry-specific association studies.

Ancestry-specific proteome-wide association studies (PWAS) based on genetically predicted protein expression can reveal complex disease etiology specific to certain ancestral groups. These studies require ancestry-specific models for protein expression as a function of SNP genotypes. In order to improve protein expression prediction in ancestral populations historically underrepresented in genomic studies, we propose a new penalized maximum likelihood estimator for fitting ancestry-specific joint protein quantitative trait loci models. Our estimator borrows information across ancestral groups, while simultaneously allowing for heterogeneous error variances and regression coefficients. We propose an alternative parameterization of our model that makes the objective function convex and the penalty scale invariant. To improve computational efficiency, we propose an approximate version of our method and study its theoretical properties. Our method provides a substantial improvement in protein expression prediction accuracy in individuals of African ancestry, and in a downstream PWAS analysis, leads to the discovery of multiple associations between protein expression and blood lipid traits in the African ancestry population.

NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations.

Commercial genome-wide genotyping arrays have historically neglected coverage of genetic variation across populations. We aimed to create a multi-ancestry genome-wide array that would include a wide range of neuro-specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies. We developed the Illumina NeuroBooster Array (NBA), a custom high-throughput and cost-effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples. This novel platform includes approximately 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease-related genome-wide association study loci across diverse populations. In this article, we describe NBA's potential as an efficient means for researchers to assess known and novel disease genetic associations in a multi-ancestry framework. The NBA can identify rare genetic variants and accurately impute more than 15 million common variants across populations. Apart from enabling sample prioritization for further whole-genome sequencing studies, we envisage that NBA will play a pivotal role in recruitment for interventional studies in the precision medicine space. From a broader perspective, the NBA serves as a promising means to foster collaborative research endeavors in the field of neurological disorders worldwide. Ultimately, this carefully designed tool is poised to make a substantial contribution to uncovering the genetic etiology underlying these debilitating conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Expanding the Russian allele frequency reference via cross-laboratory data integration: insights from 7452 exome samples.

Population allele frequency is crucially important for accurate interpretation of known and novel variants in medical genetics. Recently, several large allele frequency databases, such as the Genome Aggregation Database (gnomAD), have been created to serve as a global reference for such studies. However, frequencies of many rare alleles vary dramatically between populations, and population-specific allele frequency is often more informative than the global one. Many countries and regions, including Russia, remain poorly studied from the genetic perspective. Here, we report the first successful attempt to integrate genetic information between major medical genetic laboratories in Russia. We construct RUSeq, an open, large-scale reference set of genetic variants by analyzing 7452 exome samples collected in two major Russian cities-Moscow and St. Petersburg. An ∼10-fold increase in sample size compared to previous studies allowed us to characterize extensive genetic diversity within the admixed Russian population with contributions from several major ancestral groups. We highlight 51 known pathogenic variants that are overrepresented in Russia compared to other European countries. We also identify several dozen high-impact variants that are present in healthy donors despite being annotated as pathogenic in ClinVar and falling within genes associated with autosomal dominant disorders. The constructed database of genetic variant frequencies in Russia has been made available to the medical genetics community through a variant browser available at http://ruseq.ru.

Associations between accurate measures of adiposity and fitness, blood proteins, and insulin sensitivity among South Asians and Europeans.

South Asians (SAs) may possess a unique predisposition to insulin resistance (IR). We explored this possibility by investigating the relationship between 'gold standard' measures of adiposity, fitness, selected proteomic biomarkers, and insulin sensitivity among a cohort of SAs and Europeans (EURs). A total of 46 SAs and 41 EURs completed 'conventional' (lifestyle questionnaires, standard physical exam) as well as 'gold standard' (dual energy X-ray absorptiometry scan, cardiopulmonary exercise test, and insulin suppression test) assessments of adiposity, fitness, and insulin sensitivity. In a subset of 28 SAs and 36 EURs, we also measured the blood-levels of eleven IR-related proteins. We conducted Spearman correlation to identify correlates of steady-state plasma glucose (SSPG) derived from the insulin suppression test, followed by multivariable linear regression analyses of SSPG, adjusting for age, sex and ancestral group. Sixteen of 30 measures significantly associated with SSPG, including one conventional and eight gold standard measures of adiposity, one conventional and one gold standard measure of fitness, and five proteins. Multivariable regressions revealed that gold standard measures and plasma proteins attenuated ancestral group differences in IR, suggesting their potential utility in assessing IR, especially among SAs. Ancestral group differences in IR may be explained by accurate measures of adiposity and fitness, with specific proteins possibly serving as useful surrogates for these measures, particularly for SAs.

Polygenic risk score portability for common diseases across genetically diverse populations

BackgroundPolygenic risk scores (PRS) derived from European individuals have reduced portability across global populations, limiting their clinical implementation at worldwide scale. Here, we investigate the performance of a wide range of PRS models across four ancestry groups (Africans, Europeans, East Asians, and South Asians) for 14 conditions of high-medical interest.MethodsTo select the best-performing model per trait, we first compared PRS performances for publicly available scores, and constructed new models using different methods (LDpred2, PRS-CSx and SNPnet). We used 285 K European individuals from the UK Biobank (UKBB) for training and 18 K, including diverse ancestries, for testing. We then evaluated PRS portability for the best models in Europeans and compared their accuracies with respect to the best PRS per ancestry. Finally, we validated the selected PRS models using an independent set of 8,417 individuals from Biobank of the Americas-Genomelink (BbofA-GL); and performed a PRS-Phewas.ResultsWe confirmed a decay in PRS performances relative to Europeans when the evaluation was conducted using the best-PRS model for Europeans (51.3% for South Asians, 46.6% for East Asians and 39.4% for Africans). We observed an improvement in the PRS performances when specifically selecting ancestry specific PRS models (phenotype variance increase: 1.62 for Africans, 1.40 for South Asians and 0.96 for East Asians). Additionally, when we selected the optimal model conditional on ancestry for CAD, HDL-C and LDL-C, hypertension, hypothyroidism and T2D, PRS performance for studied populations was more comparable to what was observed in Europeans. Finally, we were able to independently validate tested models for Europeans, and conducted a PRS-Phewas, identifying cross-trait interplay between cardiometabolic conditions, and between immune-mediated components.ConclusionOur work comprehensively evaluated PRS accuracy across a wide range of phenotypes, reducing the uncertainty with respect to which PRS model to choose and in which ancestry group. This evaluation has let us identify specific conditions where implementing risk-prioritization strategies could have practical utility across diverse ancestral groups, contributing to democratizing the implementation of PRS.

Complex evolutionary patterns within the tubulin gene family of ciliates, unicellular eukaryotes with diverse microtubular structures

BackgroundTubulins are major components of the eukaryotic cytoskeletons that are crucial in many cellular processes. Ciliated protists comprise one of the oldest eukaryotic lineages possessing cilia over their cell surface and assembling many diverse microtubular structures. As such, ciliates are excellent model organisms to clarify the origin and evolution of tubulins in the early stages of eukaryote evolution. Nonetheless, the evolutionary history of the tubulin subfamilies within and among ciliate classes is unclear.ResultsWe analyzed the evolutionary pattern of ciliate tubulin gene family based on genomes/transcriptomes of 60 species covering 10 ciliate classes. Results showed: (1) Six tubulin subfamilies (α_Tub, β_Tub, γ_Tub, δ_Tub, ε_Tub, and ζ_Tub) originated from the last eukaryotic common ancestor (LECA) were observed within ciliates. Among them, α_Tub, β_Tub, and γ_Tub were present in all ciliate species, while δ_Tub, ε_Tub, and ζ_Tub might be independently lost in some species. (2) The evolutionary history of the tubulin subfamilies varied. Evolutionary history of ciliate γ_Tub, δ_Tub, ε_Tub, and ζ_Tub showed a certain degree of consistency with the phylogeny of species after the divergence of ciliate classes, while the evolutionary history of ciliate α_Tub and β_Tub varied among different classes. (3) Ciliate α- and β-tubulin isoforms could be classified into an “ancestral group” present in LECA and a “divergent group” containing only ciliate sequences. Alveolata-specific expansion events probably occurred within the “ancestral group” of α_Tub and β_Tub. The “divergent group” might be important for ciliate morphological differentiation and wide environmental adaptability. (4) Expansion events of the tubulin gene family appeared to be consistent with whole genome duplication (WGD) events in some degree. More Paramecium-specific tubulin expansions were detected than Tetrahymena-specific ones. Compared to other Paramecium species, the Paramecium aurelia complex underwent a more recent WGD which might have experienced more tubulin expansion events.ConclusionsEvolutionary history among different tubulin gene subfamilies seemed to vary within ciliated protists. And the complex evolutionary patterns of tubulins among different ciliate classes might drive functional diversification. Our investigation provided meaningful information for understanding the evolution of tubulin gene family in the early stages of eukaryote evolution.

Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks.

The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings. Heart rate, platelet count, bone mineral density and many other traits show stratification similar to height and pigmentation traits, likely targets of selection and divergence across ancestral groups. We show that the reported ancestry-trait associations are not driven by environmental confounders by confirming our results when using between-sibling differences in ancestry. The consistency of our results across biobanks further supports this and indicates that these genetic predispositions that derive from post-Neolithic admixture events act as a source of variability and as potential confounders in Europe as a whole.

Perspectives from cystinosis: access to healthcare may be a confounding factor for variant classification.

Genetic variability persists across diverse populations, and it may impact the characterization of heritable diseases in different ancestral groups. Cystinosis is a metabolic disease caused by pathogenic variants in the CTNS gene causing the cellular accumulation of cystine. We attempted to assess the currently poorly characterized prevalence of cystinosis by employing a population genetics methodology. However, we encountered a significant challenge due to genetic variations across different populations, and the consideration of potential disparities in access to healthcare made our results inconclusive. Pathogenic CTNS variants were identified in a representative global population cohort using The Human Gene Mutation Database (HGMD) and the 1000 Genomes (1KG) database. The c.124G>A (p.Val42Ile) variant was reported to be pathogenic based on an observation in the white population presenting with atypical phenotypes, but it would be reclassified as benign in the African ancestral group if applying the ACMG allele frequency guideline due to its high allele frequency specifically in this population. Inclusion or exclusion of this c.124G>A (p.Val42Ile) variant results in a significant change in estimated disease prevalence, which can impact the diagnosis and treatment of affected patients with a broad range of phenotypic presentations. This observation led us to postulate that pathogenic manifestations of the disease may be underdiagnosed due to variable expressivity and systemic inequities in access to care, specifically in the African subpopulation. We call for a more cautious and inclusive approach to achieve more equitable care across diverse populations.

Epidemiology of Huntington's Disease in Latin America: A Systematic Review and Meta-Analysis.

Latin America has played a crucial role in advancing our understanding of Huntington's disease (HD). However, previous global reviews include limited data from Latin America. It is possible that English-based medical search engines may not capture all the relevant studies. We searched databases in Spanish, Portuguese, and English. The names of every country in Latin America in English-based search engines were used to ensure we found any study that had molecular ascertainment and provided general epidemiological information or subpopulation data. Additionally, we contacted experts across the region. The search strategy yielded 791 citations; 24 studies met inclusion criteria, representing 12 of 36 countries. The overall pooled prevalence was 0.64 per 100,000 (prediction interval, 0.06-7.22); for cluster regions, it was 54 per 100,000 (95% CI, 34.79-84.92); for juvenile HD, it was 8.7% (prediction interval, 5.12-14.35), and 5.9% (prediction interval, 2.72-13.42) for late-onset HD. The prevalence was higher for Mexico, Peru, and Brazil. However, there were no significant differences between Central America and the Caribbean versus South America. The prevalence of HD appears to be similar across Latin America. However, we infer that our findings are underestimates, in part because of limited research and underdiagnosis of HD because of limited access to molecular testing and the availability of neurologists and movement disorders specialists. Future research should focus on identifying pathways to improve access to molecular testing and education and understanding differences among different ancestral groups in Latin America. © 2024 International Parkinson and Movement Disorder Society.

Effect of FADS1 SNPs rs174546, rs174547 and rs174550 on blood fatty acid profiles and plasma free oxylipins.

Previous studies have indicated that activity of fatty acid desaturase 1 (FADS1), is involved in cardiometabolic risk. Recent experimental data have shown that FADS1 knockdown can promote lipid accumulation and lipid droplet formation in liver cells. In this study, we aimed to characterize whether different FADS1 genotypes affect liver fat content, essential fatty acid content and free oxylipin mediators in the blood. We analyzed the impact of FADS1 single-nucleotide polymorphisms (SNPs) rs174546, rs174547, and rs174550 on blood fatty acids and free oxylipins in a cohort of 85 patients from an academic metabolic medicine outpatient center. Patients were grouped based on their genotype into the homozygous major (derived) allele group, the heterozygous allele group, and the homozygous minor (ancestral) allele group. Omega-3 polyunsaturated fatty acids (n-3 PUFA) and omega-6 polyunsaturated fatty acids (n-6 PUFA) in the blood cell and plasma samples were analyzed by gas chromatography. Free Oxylipins in plasma samples were analyzed using HPLC-MS/MS. Liver fat content and fibrosis were evaluated using Fibroscan technology. Patients with the homozygous ancestral (minor) FADS1 genotype exhibited significantly lower blood levels of the n-6 PUFA arachidonic acid (AA), but no significant differences in the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There were no significant differences in liver fat content or arachidonic acid-derived lipid mediators, such as thromboxane B2 (TXB2), although there was a trend toward lower levels in the homozygous ancestral genotype group. Our findings suggest that FADS1 genotypes influence the blood levels of n-6 PUFAs, while not significantly affecting the n-3 PUFAs EPA and DHA. The lack of significant differences in liver fat content and arachidonic acid-derived lipid mediators suggests that the genotype-related variations in fatty acid levels may not directly translate to differences in liver fat or inflammatory lipid mediators in this cohort. However, the trend towards lower levels of certain lipid mediators in the homozygous ancestral genotype group warrants further investigation to elucidate the underlying mechanisms of different FADS1 genotypes and potential implications for cardiometabolic risk.

Comparing the frequency of variants of uncertain significance (VUS) between ancestry groups in a paediatric epilepsy cohort

BackgroundStudies indicate that variants of uncertain significance are more common in non-European populations due to lack of a diversity in population databases. This difference has not been explored in epilepsy,...

Alterations in pharmacogenetic genes and their implications for imatinib resistance in Chronic Myeloid Leukemia patients from an admixed population.

Imatinib is the tyrosine kinase inhibitor used as the gold standard for the treatment of Chronic Myeloid Leukemia. However, about 30% of patients do not respond well to this therapy. Variants in drug administration, distribution, metabolism and excretion (ADME) genes play an important role in drug resistance especially in admixed populations. We investigated 129 patients diagnosed with Chronic Myeloid Leukemia treated with imatinib as first choice therapy. The participants of the study are highly admixed, populations that exhibit genetic diversity and complexity due to the contributions of multiple ancestral groups. Thus, the aim of this work was to investigate the association of 30 SNVs in genes related to response to treatment with Imatinibe in CML. Our results indicated that for the rs2290573 of the ULK3 gene, patients with the recessive AA genotype are three times more likely to develop resistance over time (secondary resistance) (p = 0.019, OR = 3.19, IC 95%= 1.21-8.36). Finally, we performed interaction analysis between the investigated variants and found several associations between SNVs and secondary resistance. We concluded that the variant rs2290573 of the ULK3 gene may be relevant for predicting treatment response of CML with imatinib, as well as possible treatment resistance. The use of predictive biomarkers is an important tool for therapeutic choice of patients, improving their quality of life and treatment efficacy.

Novel Rickettsia and host records for argasid ticks, including Alveonasus cooleyi, on wild mammals in Baja California, Mexico.

We conducted surveillance of mammals to investigate their associations with argasid ticks and tick-borne pathogens. During 2021, a total of 20 wild carnivores and 57 lagomorphs were sampled, and 39 argasid ticks belonging to two species were collected. All mammals and ticks were tested by molecular assays to detect Borrelia and Rickettsia infections. Nine ticks identified as Otobius megnini were collected from two coyotes (Canis latrans) and 30 Alveonasus cooleyi (McIvor 1941) were collected from six bobcats (Lynx rufus) and one rabbit (Sylvilagus auduboni). We detected Rickettsia spp. DNA in 21 of the 27 (77.8%) tested Av. cooleyi and none of the O. megnini. No ticks were PCR-positive for borreliae and all mammals were PCR-negative for both pathogen genera. Phylogenetic analysis based on gltA, htrA, and 16S rRNA targets revealed that all rickettsiae from Av. cooleyi clustered with ancestral group rickettsiae, likely representing a novel species of possibly endosymbiotic Rickettsia. The significance of Av. cooleyi and the newly identified Rickettsia sp. to the health of wildlife is unknown, and further work is indicated to determine whether they may be relevant to public health or carnivore conservation.

Harnessing landrace diversity empowers wheat breeding

Harnessing genetic diversity in major staple crops through the development of new breeding capabilities is essential to ensure food security1. Here we examined the genetic and phenotypic diversity of the A. E. Watkins landrace collection2 of bread wheat (Triticum aestivum), a major global cereal, by whole-genome re-sequencing of 827 Watkins landraces and 208 modern cultivars and in-depth field evaluation spanning a decade. We found that modern cultivars are derived from two of the seven ancestral groups of wheat and maintain very long-range haplotype integrity. The remaining five groups represent untapped genetic sources, providing access to landrace-specific alleles and haplotypes for breeding. Linkage disequilibrium-based haplotypes and association genetics analyses link Watkins genomes to the thousands of identified high-resolution quantitative trait loci and significant marker–trait associations. Using these structured germplasm, genotyping and informatics resources, we revealed many Watkins-unique beneficial haplotypes that can confer superior traits in modern wheat. Furthermore, we assessed the phenotypic effects of 44,338 Watkins-unique haplotypes, introgressed from 143 prioritized quantitative trait loci in the context of modern cultivars, bridging the gap between landrace diversity and current breeding. This study establishes a framework for systematically utilizing genetic diversity in crop improvement to achieve sustainable food security.

Genomic insights into hybrid zone formation: The role of climate, landscape, and demography in the emergence of a novel hybrid lineage.

Population demographic changes, alongside landscape, geographic and climate heterogeneity, can influence the timing, stability and extent of introgression where species hybridise. Thus, quantifying interactions across diverged lineages, and the relative contributions of interspecific genetic exchange and selection to divergence at the genome-wide level is needed to better understand the drivers of hybrid zone formation and maintenance. We used seven latitudinally arrayed transects to quantify the contributions of climate, geography and landscape features to broad patterns of genetic structure across the hybrid zone of Populus trichocarpa and P. balsamifera and evaluated the demographic context of hybridisation over time. We found genetic structure differed among the seven transects. While ancestry was structured by climate, landscape features influenced gene flow dynamics. Demographic models indicated a secondary contact event may have influenced contemporary hybrid zone formation with the origin of a putative hybrid lineage that inhabits regions with higher aridity than either of the ancestral groups. Phylogenetic relationships based on chloroplast genomes support the origin of this hybrid lineage inferred from demographic models based on the nuclear data. Our results point towards the importance of climate and landscape patterns in structuring the contact zones between P. trichocarpa and P. balsamifera and emphasise the value whole genome sequencing can have to advancing our understanding of how neutral processes influence divergence across space and time.

Why we thrive beneath a northern sky – genomic signals of selection in apple for adaptation to northern Sweden

Good understanding of the genomic regions underlying adaptation of apple to boreal climates is needed to facilitate efficient breeding of locally adapted apple cultivars. Proper infrastructure for phenotyping and evaluation is essential for identification of traits responsible for adaptation, and dissection of their genetic composition. However, such infrastructure is costly and currently not available for the boreal zone of northern Sweden. Therefore, we used historical pomological data on climate adaptation of 59 apple cultivars and whole genome sequencing to identify genomic regions that have undergone historical selection among apple cultivars recommended for cultivation in northern Sweden. We found the apple collection to be composed of two ancestral groups that are largely concordant with the grouping into ‘hardy’ and ‘not hardy’ cultivars based on the pomological literature. Using a number of genome-wide scans for signals of selection, we obtained strong evidence of positive selection at a genomic region around 29 MbHFTH1 of chromosome 1 among apple cultivars in the ‘hardy’ group. Using phased genotypic data from the 20 K apple Infinium® SNP array, we identified haplotypes associated with the two cultivar groups and traced transmission of these haplotypes through the pedigrees of some apple cultivars. This demonstrates that historical data from pomological literature can be analyzed by population genomic approaches as a step towards revealing the genomic control of a key property for a horticultural niche market. Such knowledge is needed to facilitate efficient breeding strategies for development of locally adapted apple cultivars in the future. The current study illustrates the response to a very strong selective pressure imposed on tree crops by climatic factors, and the importance of genetic research on this topic and feasibility of breeding efforts in the light of the ongoing climate change.

Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution.

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.